{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:13:45Z","timestamp":1791328425396,"version":"4.3.1"},"reference-count":27,"publisher":"American Diabetes Association","issue":"9","license":[{"start":{"date-parts":[[2022,7,11]],"date-time":"2022-07-11T00:00:00Z","timestamp":1657497600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"funder":[{"name":"Lexicon Pharmaceuticals, Inc"},{"DOI":"10.13039\/100004339","name":"Sanofi","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004339","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,9,1]]},"abstract":"<jats:sec>\n                    <jats:title>OBJECTIVE<\/jats:title>\n                    <jats:p>Inhibiting sodium\u2013glucose cotransporters (SGLTs) improves glycemic and cardiovascular outcomes in patients with type 2 diabetes (T2D). We investigated the differential impact of selective SGLT2 inhibition and dual inhibition of SGLT1 and SGLT2 on multiple parameters.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                    <jats:p>Using a double-blind, parallel-group design, we randomized 40 patients with T2D and hypertension to receive the dual SGLT1 and SGLT2 inhibitor sotagliflozin 400 mg or the selective SGLT2 inhibitor empagliflozin 25 mg, with preexisting antihypertensive treatment, for 8 weeks. In an in-house testing site, mixed-meal tolerance tests (MMTTs) and other laboratory and clinical evaluations were used to study metabolic, intestinal, cardiovascular, and urinary parameters over 24 h.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Changes from baseline in glycemic and blood pressure control; intestinal, urine, and metabolic parameters; and cardiovascular biomarkers were generally similar with sotagliflozin and empagliflozin. During the breakfast MMTT, sotagliflozin significantly reduced incremental area under the curve (AUC) values for postprandial glucose, insulin, and glucose-dependent insulinotropic polypeptide (GIP) and significantly increased incremental AUCs for postprandial glucagon-like peptide 1 (GLP-1) relative to empagliflozin, consistent with sotagliflozin-mediated inhibition of intestinal SGLT1. These changes waned during lunch and dinner MMTTs. Both treatments significantly lowered GIP incremental AUCs relative to baseline over the 14 h MMTT interval; the most vigorous effect was seen with sotagliflozin soon after start of the first meal of the day. No serious or severe adverse events were observed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>Changes from baseline in glycemic and blood pressure control, cardiovascular biomarkers, and other parameters were comparable between sotagliflozin and empagliflozin. However, sotagliflozin but not empagliflozin inhibited intestinal SGLT1 after breakfast as shown by larger changes in postprandial glucose, insulin, GIP, and GLP-1 AUCs, particularly after breakfast. Additional study is warranted to assess the clinical relevance of transient SGLT1 inhibition and differences in incretin responses (NCT03462069).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2337\/dc21-2166","type":"journal-article","created":{"date-parts":[[2022,7,11]],"date-time":"2022-07-11T18:28:15Z","timestamp":1657564095000},"page":"2118-2126","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":34,"title":["Metabolic, Intestinal, and Cardiovascular Effects of Sotagliflozin Compared With Empagliflozin in Patients With Type 2 Diabetes: A Randomized, Double-Blind Study"],"prefix":"10.2337","volume":"45","author":[{"given":"Maximilian G.","family":"Posch","sequence":"first","affiliation":[{"name":"1Charit\u00e9 Research Organisation GmbH, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2102-5835","authenticated-orcid":false,"given":"Niklas","family":"Walther","sequence":"additional","affiliation":[{"name":"1Charit\u00e9 Research Organisation GmbH, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ele","family":"Ferrannini","sequence":"additional","affiliation":[{"name":"2National Research Council Institute of Clinical Physiology, Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Powell","sequence":"additional","affiliation":[{"name":"3Lexicon Pharmaceuticals, Inc., The Woodlands, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip","family":"Banks","sequence":"additional","affiliation":[{"name":"3Lexicon Pharmaceuticals, Inc., The Woodlands, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suman","family":"Wason","sequence":"additional","affiliation":[{"name":"3Lexicon Pharmaceuticals, Inc., The Woodlands, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphael","family":"Dahmen","sequence":"additional","affiliation":[{"name":"4Sanofi, Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2022,7,11]]},"reference":[{"key":"2023053115104164500_B1","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1002\/ejhf.1954","article-title":"Sodium-glucose co-transporter 2 inhibitors in heart failure: beyond glycaemic control. A position paper of the Heart Failure Association of the European Society of Cardiology","volume":"22","author":"Seferovi\u0107","year":"2020","journal-title":"Eur J Heart Fail"},{"key":"2023053115104164500_B2","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1016\/j.jacbts.2020.02.004","article-title":"Mechanisms of cardiovascular benefits of sodium glucose co-transporter 2 (SGLT2) inhibitors: a state-of-the-art review","volume":"5","author":"Lopaschuk","year":"2020","journal-title":"JACC Basic Transl Sci"},{"key":"2023053115104164500_B3","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1517\/13543784.2015.1100361","article-title":"Sotagliflozin as a potential treatment for type 2 diabetes mellitus","volume":"24","author":"Cariou","year":"2015","journal-title":"Expert Opin Investig Drugs"},{"key":"2023053115104164500_B4","doi-asserted-by":"crossref","first-page":"1970","DOI":"10.2337\/dc18-0343","article-title":"Sotagliflozin in combination with optimized insulin therapy in adults with type 1 diabetes: the North American inTandem1 Study","volume":"41","author":"Buse","year":"2018","journal-title":"Diabetes Care"},{"key":"2023053115104164500_B5","doi-asserted-by":"crossref","first-page":"1981","DOI":"10.2337\/dc18-0342","article-title":"HbA1c and hypoglycemia reduction at 24 and 52 weeks with sotagliflozin in combination with insulin in adults with type 1 diabetes: the European inTandem2 study","volume":"41","author":"Danne","year":"2018","journal-title":"Diabetes Care"},{"key":"2023053115104164500_B6","doi-asserted-by":"crossref","first-page":"2337","DOI":"10.1056\/NEJMoa1708337","article-title":"Effects of sotagliflozin added to insulin in patients with type 1 diabetes","volume":"377","author":"Garg","year":"2017","journal-title":"N Engl J Med"},{"key":"2023053115104164500_B7","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1038\/clpt.2012.58","article-title":"LX4211, a dual SGLT1\/SGLT2 inhibitor, improved glycemic control in patients with type 2 diabetes in a randomized, placebo-controlled trial","volume":"92","author":"Zambrowicz","year":"2012","journal-title":"Clin Pharmacol Ther"},{"key":"2023053115104164500_B8","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1056\/NEJMoa2030183","article-title":"Sotagliflozin in patients with diabetes and recent worsening heart failure","volume":"384","author":"Bhatt","year":"2021","journal-title":"N Engl J Med"},{"key":"2023053115104164500_B9","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1056\/NEJMoa2030186","article-title":"Sotagliflozin in patients with diabetes and chronic kidney disease","volume":"384","author":"Bhatt","year":"2021","journal-title":"N Engl J Med"},{"key":"2023053115104164500_B10","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.clinthera.2014.10.026","article-title":"LX4211 therapy reduces postprandial glucose levels in patients with type 2 diabetes mellitus and renal impairment despite low urinary glucose excretion","volume":"37","author":"Zambrowicz","year":"2015","journal-title":"Clin Ther"},{"key":"2023053115104164500_B11","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1124\/jpet.113.203364","article-title":"LX4211 increases serum glucagon-like peptide 1 and peptide YY levels by reducing sodium\/glucose cotransporter 1 (SGLT1)-mediated absorption of intestinal glucose","volume":"345","author":"Powell","year":"2013","journal-title":"J Pharmacol Exp Ther"},{"key":"2023053115104164500_B12","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1124\/jpet.114.214304","article-title":"Effect of LX4211 on glucose homeostasis and body composition in preclinical models","volume":"350","author":"Powell","year":"2014","journal-title":"J Pharmacol Exp Ther"},{"key":"2023053115104164500_B13","doi-asserted-by":"crossref","first-page":"e1235","DOI":"10.1210\/clinem\/dgz258","article-title":"Sotagliflozin decreases postprandial glucose and insulin concentrations by delaying intestinal glucose absorption","volume":"105","author":"Powell","year":"2020","journal-title":"J Clin Endocrinol Metab"},{"key":"2023053115104164500_B14","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1007\/s00125-020-05093-9","article-title":"Glucose-dependent insulinotropic peptide and risk of cardiovascular events and mortality: a prospective study","volume":"63","author":"Juji\u0107","year":"2020","journal-title":"Diabetologia"},{"key":"2023053115104164500_B15","doi-asserted-by":"crossref","first-page":"239","DOI":"10.2337\/db15-0122","article-title":"Glucose-dependent insulinotropic polypeptide stimulates osteopontin expression in the vasculature via endothelin-1 and CREB","volume":"65","author":"Berglund","year":"2016","journal-title":"Diabetes"},{"key":"2023053115104164500_B16","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.cmet.2017.11.003","article-title":"Inactivation of the glucose-dependent insulinotropic polypeptide receptor improves outcomes following experimental myocardial infarction","volume":"27","author":"Ussher","year":"2018","journal-title":"Cell Metab"},{"key":"2023053115104164500_B17","doi-asserted-by":"crossref","first-page":"101090","DOI":"10.1016\/j.molmet.2020.101090","article-title":"Glucagon-like peptide-1 receptor co-agonists for treating metabolic disease","volume":"46","author":"Baggio","year":"2021","journal-title":"Mol Metab"},{"key":"2023053115104164500_B18","doi-asserted-by":"crossref","first-page":"e2710","DOI":"10.1210\/clinem\/dgaa327","article-title":"GIP as a therapeutic target in diabetes and obesity: insight from incretin co-agonists","volume":"105","author":"Holst","year":"2020","journal-title":"J Clin Endocrinol Metab"},{"key":"2023053115104164500_B19","doi-asserted-by":"crossref","first-page":"bnz002","DOI":"10.1210\/endrev\/bnz002","article-title":"Glucose-dependent insulinotropic polypeptide receptor therapies for the treatment of obesity, do agonists = antagonists?","volume":"41","author":"Killion","year":"2020","journal-title":"Endocr Rev"},{"key":"2023053115104164500_B20","doi-asserted-by":"crossref","first-page":"2344","DOI":"10.2337\/dc15-0642","article-title":"Sodium-glucose cotransporter inhibitors: effects on renal and intestinal glucose transport: from bench to bedside","volume":"38","author":"Mudaliar","year":"2015","journal-title":"Diabetes Care"},{"key":"2023053115104164500_B21","doi-asserted-by":"crossref","first-page":"3021","DOI":"10.1093\/eurheartj\/ehy339","article-title":"2018 ESC\/ESH Guidelines for the management of arterial hypertension","volume":"39","author":"Williams","year":"2018","journal-title":"Eur Heart J"},{"key":"2023053115104164500_B22","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/1742-4682-11-33","article-title":"Optimal back-extrapolation method for estimating plasma volume in humans using the indocyanine green dilution method","volume":"11","author":"Polidori","year":"2014","journal-title":"Theor Biol Med Model"},{"key":"2023053115104164500_B23","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1016\/j.jacc.2018.07.061","article-title":"Genetic variants in SGLT1, glucose tolerance, and cardiometabolic risk","volume":"72","author":"Seidelmann","year":"2018","journal-title":"J Am Coll Cardiol"},{"key":"2023053115104164500_B24","doi-asserted-by":"crossref","first-page":"E117","DOI":"10.1152\/ajpendo.00439.2012","article-title":"Improved glycemic control in mice lacking Sglt1 and Sglt2","volume":"304","author":"Powell","year":"2013","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"2023053115104164500_B25","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.cmet.2017.04.011","article-title":"Sodium-glucose co-transporters and their inhibition: clinical physiology","volume":"26","author":"Ferrannini","year":"2017","journal-title":"Cell Metab"},{"key":"2023053115104164500_B26","doi-asserted-by":"crossref","first-page":"771","DOI":"10.2337\/dc16-2724","article-title":"Renal handling of ketones in response to sodium-glucose cotransporter 2 inhibition in patients with type 2 diabetes","volume":"40","author":"Ferrannini","year":"2017","journal-title":"Diabetes Care"},{"key":"2023053115104164500_B27","doi-asserted-by":"crossref","first-page":"2098","DOI":"10.1007\/s00125-018-4669-0","article-title":"The actions of SGLT2 inhibitors on metabolism, renal function and blood pressure","volume":"61","author":"Thomas","year":"2018","journal-title":"Diabetologia"}],"container-title":["Diabetes Care"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/45\/9\/2118\/716091\/dc212166.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/45\/9\/2118\/716091\/dc212166.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,31]],"date-time":"2023-05-31T11:11:19Z","timestamp":1685531479000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/care\/article\/45\/9\/2118\/147215\/Metabolic-Intestinal-and-Cardiovascular-Effects-of"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,11]]},"references-count":27,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2022,7,11]]},"published-print":{"date-parts":[[2022,9,1]]}},"URL":"https:\/\/doi.org\/10.2337\/dc21-2166","relation":{},"ISSN":["0149-5992"],"issn-type":[{"value":"0149-5992","type":"print"}],"subject":[],"published":{"date-parts":[[2022,7,11]]}}}